Anti-Proliferative And Anti-Inflammatory Agent Combination For Treatment Of Vascular Disorders With An Implantable Medical Device

Abstract

Drug-delivery systems such as drug-delivery stents having an anti-proliferative agent such as everolimus and an anti-flammatory agent such as clobetasol are provided. Also disclosed are methods of treating a vascular impairment such as restenosis or vulnerable plaque

Description

CROSS-REFERENCE[0001]This is a continuation-in-part of application Ser. No. 11 / 090,507 filed on Mar. 24, 2005 which is a continuation-in-part of application Ser. No. 10 / 882,506 filed on Jun. 30, 2004, both of which are incorporated by reference herein.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]This invention generally relates to a drug combination including an anti-proliferative drug such as everolimus and an anti-inflammatory agent such as clobetasol for the treatment of a disorder such as restenosis and vulnerable plaque.[0004]2. Description of the Background[0005]Plaques have been associated with stenosis and restenosis. While treatments of plaque-induced stenosis and restenosis have advanced significantly over the last few decades, the morbidity and mortality associated with vascular plaques have remained significant. Recent work suggests that plaque may generally fall into one of two different general types: standard stenotic plaques and vulnerable plaques....

AI Technical Summary

Benefits of technology

[0011]Various embodiments of the present invention include a drug-delivery system, comprising: an effective amount of an anti-proliferative agent; a body structure of an implantable medical device comprising at least one depot within the body structure, wherein the at least one depot has an opening on a surface of the body structure and a depth within the body structure; and an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent deposited within the depot for the treatment of a vascular disorder or a related disorder; wherein the anti-proliferative agent is everolimus and the steroidal or non-steroidal anti-inflammatory agent is clobetasol, and wherein the ratio of the dose of everolimus to the dose of clobetasol is 1:1 to 3:1 on a molar basis.

[0012]Further embodiments of the present invention include a method of treating restenosis or vulnerable plaque of a blood vessel comprising: administering to a patient an effective amount of an anti-proliferative agent; and allowing an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent to elute to a vessel from within at least one depot within a body structure of an implantable medical device, wherein the at least one depot has an opening on a surface of the body structure and a depth within the body structure, wherein the combination of the anti-proliferative and anti-inflammatory agents is for treatment of restenosis or vulnerable plaque; wherein the anti-proliferative agent is everolimus and the steroidal or non-steroidal anti-inflammatory agent is clobetasol, and wherein the ratio of the dose of everolimus to the dose of clobetasol is 1:1 to 3:1 on a molar basis.

[0013]Additional embodiments of the present invention include a stent, comprising: an effective amount of an anti-proliferative agent; a body structure of an implantable medical device; and an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent mixed or dispersed throughout the body structure of the stent for the treatment of a vascular disorder or a related disorder.

[0014]Other embodiments of the present invention include a method of treating restenosis or vulnerable plaque of a blood vessel comprising: implanting a stent in a blood vessel, wherein the stent comprises a scaffolding structure made of a bioabsorbable polymer, wherein an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent is mixed or dispersed throughout the scaffolding structure; administering to a patient an effective amount of an anti-proliferative agent; and allowing an effective amount of a steroidal anti-inflammatory agent or a non steroidal anti-inflammatory agent to elute to a vessel from a body structure, wherein the combination of the anti-proliferative and anti-inflammatory agents is for treatment of restenosis or vulnerable plaque.

Problems solved by technology

While treatments of plaque-induced stenosis and restenosis have advanced significantly over the last few decades, the morbidity and mortality associated with vascular plaques have remained significant.

Unfortunately, as plaque matures, narrowing of a blood vessel by a proliferation of smooth muscle cells, matrix synthesis, and lipid accumulation may result in formation of a plaque which is quite different than a standard stenotic plaque.

Such atherosclerotic plaque becomes thrombosis-prone, and can be highly dangerous.

While the known procedures for treating plaque have gained wide acceptance and have shown good efficacy for treatment of standard stenotic plaques, they may be ineffective (and possibly dangerous) when thrombotic conditions are superimposed on atherosclerotic plaques.

Specifically, mechanical stresses caused by primary treatments like percutaneous transluminal intervention (PTI), such as stenting, may actually trigger release of fluids and / or solids from a vulnerable plaque into the blood stream, thereby potentially causing a coronary thrombotic occlusion.

There is evidence that fibrous cap can be ruptured during stent deployment.

However, one of the major clinical challenges of bioabsorbable stents is adequately suppressing acute or chronic inflammatory responses triggered by the degradation of the stent.

Anti-proliferative drugs are often sufficient to reduce neointimal formation, but do not have the ability to adequately suppress inflammation.

Images